Addressing Cumulative Risk in the Occupational Environment

in Combination
Cumulative risk assessment, or CRA, is the analysis and characterization of the combined risks to human health associated with co-exposures to numerous stressors. This developing area emphasizes the need to understand the joint exposures and possible interactions among a wide range of potential stressors, including chemicals, physical agents, biological agents, and social and psychosocial risk factors. Unlike traditional risk assessment approaches, which typically focus on a single chemical stressor released in the environment, CRA begins by identifying populations of interest, such as a specific community or worker group, and then determines the combination of stressors or other risk factors that may affect these groups.

CRAs have been conducted to address large, complex issues where the interactions among stressors may increase risks to human health in the general population. Two published examples of this type of CRA include an assessment of cumulative cancer risk from air pollution, which appeared in a 2008 issue of
Environmental Science & Technology
(ES&T), and an investigation of the interaction between chronic stress, race/ethnicity, and neurotoxicants (lead and methyl mercury), which appeared in the
International Journal of Environmental Research and Public Health
in 2014. Because such applications more fully characterize different stressors involved in the situation under study, these CRAs provide a more realistic assessment of total health impact. The CRA approach also improves our ability to identify the contribution of various factors to overall risk, helping us make better decisions when choosing among strategies for risk mitigation.
Unfortunately, the majority of CRAs conducted to date have not considered occupational exposures and workplace stressors that can affect human health. This is an important limitation. Occupational risk factors, such as workplace conditions and exposures to chemical and non-chemical stressors, have long been recognized to affect worker health and well-being. Because workers often face a disproportionate risk compared to the general public due to greater exposures in occupational settings, “workers” were recently designated as a “susceptible population” in the 2016 Frank R. Lautenberg Chemical Safety for the 21st Century Act, which updates the 1976 Toxic Substances Control Act. Although this designation applies only to chemical exposures, workers frequently encounter unique conditions and hazards beyond chemicals that contribute to their cumulative risk for adverse effects.
Recent publications in ES&T and the
Journal of Occupational and Environmental Hygiene
have advocated for better integration or consideration of occupational risk factors in future CRAs. The CRA approach may also prove useful for linking traditional occupational risk assessments to the goals and objectives of the NIOSH Total Worker Health program and help redefine the focus and scope of occupational risk assessments. However, despite the potential of CRA, there are many practical challenges to implementing these approaches in occupational health. Based on several presentations at conferences held by AIHA and the Society for Risk Analysis, this article highlights some key challenges hindering the wider use of occupationally-based CRAs and presents some existing methods and tools that can be modified to advance this approach in the near term while additional research is developed.
Limited exposure data are available regarding many of the types of non-chemical stressors (including personal or lifestyle factors) that might be important to consider in an occupationally-based CRA.
Eight Activities Needed to Advance the Application of CRA in the Workplace
  1. Develop a unified glossary of exposure and risk terms and definitions for use in occupationally-based CRAs.
  2. Establish a tiered decision-making framework for inclusion of different exposure and risk factors from occupational and non-occupational domains.
  3. Create an accessible (publicly available) database clearinghouse that contains data on exposure and risk factors most relevant for different occupational settings.
  4. Integrate and expand on existing data sets and tools used in other settings for use in occupational settings.
  5. Conduct occupationally-based feasibility studies to determine the most important data gaps and research needs for future CRA development.
  6. Develop and publish case study examples where CRA can or should be used to better characterize occupational risks.
  7. Develop interactive (web-based) educational tools that can be used to conduct, interpret, and communicate the results of CRAs.
  8. Prepare ethical standards for including personal and other data into CRAs conducted in occupational settings.
CRAs in occupational settings are hindered by many of the same methodological and technical challenges as complex risk assessments encountered in environmental or community settings. However, due to standard practices, regulatory frameworks, privacy issues, employer responsibilities, and other factors, there are additional challenges unique to the workplace. Some of the key challenges include:
Methodological limitations.
A uniform framework for assessing occupational risks using a CRA approach has not yet been developed. It is therefore difficult to determine which stressors, worker groups, and health effects should be considered in a CRA. Current occupational risk assessments typically measure exposure to a single chemical or stressor and then compare that exposure to an occupational exposure limit (OEL) developed specifically for that chemical or stressor. OELs for different types of stressors are usually defined using different exposure metrics. Moving to a more complex system would require alternative tools for measuring, characterizing, or setting limits for combined exposures. Because validated benchmarks or limits for complex mixtures currently do not exist, industrial hygienists continue to rely on traditional dose addition formulas.
Data and information gaps.
Limited exposure data are available regarding many of the types of non-chemical stressors (including personal or lifestyle factors) that might be important to consider in an occupationally-based CRA. There are also limited data on internal dose measurements for workers in different settings and few indices of useful biomarkers of exposure. In addition, there are very limited data specifically evaluating the health consequences of mixed exposures where the levels of each stressor are measured quantitatively. The examples where such analyses have been explored generally address only one or two factors at a time, such as the effects of co-exposures to toluene and noise on hearing loss or smoking and asbestos on lung cancer risk.
Regulatory and public policy constraints.
To be optimally informative for risk prioritization and risk management, CRAs should account for the most important exposures arising from any domain (occupational and non-occupational). However, current regulatory frameworks focus primarily on a specific domain; for example, there are separate frameworks for occupational, environmental, and consumer safety regulations. This has led to a “silo effect”: recommendations that focus on a specific domain and don’t consider or account for external risk factors that arise from other domains. It’s clear that exposures to stressors occur across different domains, and that the combined exposures affect human health. But the structural barriers built into the regulatory framework hamper communication and application of risk mitigation.
Social and ethical considerations.
The use of novel or invasive approaches to obtain data in occupational settings (for example, completing detailed questionnaires, collecting biological specimens) raises questions related to worker privacy and access to or misuse of personal data. The consideration of non-occupational risk factors in a CRA also raises liability concerns and questions about the role of the employer and employee in limiting risks where the total risk arises from interactions of non-work and work-related exposures. In addition, the collection of new information is likely to lead to greater need for employee communication and education. How such issues are addressed will vary between organizations and reflect their culture and tolerance of risk.
Figure 1. Accounting for cumulative risks using the current IH paradigm.
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Although there are many challenges in conducting a comprehensive formal CRA, industrial hygienists can take some steps to move toward CRA implementation and align with current occupational risk assessment practice (see Figure 1). Ways to incorporate CRA perspectives include:
Use of mode of action (MOA) hypotheses to identify potential stressors and their interactions.
MOA is the use of toxicology and physiology to identify the way a stressor affects human health. Using this concept, IHs can survey the workplace to identify potential combined stressor exposures that might be particularly problematic. Dusting off the toxicology textbook will go a long way toward developing such a hazard characterization. For example, if screening a list of materials present in a work task during the job hazard analysis (JHA) shows significant potential exposure to nervous system toxicants such as solvents, then extra scrutiny to identify physiological stressors like fatigue would be warranted. If exposures involve cardiotoxic materials, then activities that require extensive cardiovascular stress would merit review. It’s important to note that in each of these cases the individual stressors would be managed below their respective limits per traditional industrial hygiene practice, but the goal is to go beyond that traditional approach to systematically consider and document potential interactions that are unaccounted for.
Use checklist and audit tools to identify interactive stressors in the workplace and beyond.
Because the potential for interactions is complex, and in many workplaces the number of potential hazards (stressors) is large, a systematic tool to supplement the traditional JHA would be very helpful. Such a tool was proposed in a presentation at the 2014 annual meeting of the
Society of Toxicology
. The tool lists identified stressors, their routes of exposure, mode of toxic action, and potential for interactions. The tool can vary in complexity and level of documentation. The primary goal is to ensure that combinations of stressors are specifically evaluated as part of the JHA process.
Adjust OELs to incorporate scenario- and population-specific susceptibility factors, including non-occupational stressors.
To date, the primary quantitative risk characterization tool used by the IH is the occupational exposure limit. In most cases, the OEL does not consider unique CRA needs for the scenario for which it is applied. Instead, OELs are intended to be generally applicable limits that include an in-depth review of the toxicity profile for the chemical or hazard irrespective of site-specific exposure scenarios. Thus, the OEL can be viewed as a starting point that can be adjusted, based on the IH’s professional judgment, to take into consideration other factors in the environmental or occupational scenario.
One mechanism for adjusting the OEL is the establishment of a JHA or site-specific action level (AL). The IH would interpret the OEL based on site-specific factors so that the AL is set below the OEL. This could be accomplished through two approaches. The first approach would require reducing the AL based on non-work-related exposures common in the work force that might increase susceptibility to the toxicity of the agent under concern. The second approach would account for potential cumulative risks due to workplace exposure or interactions. In both approaches, the IH would need to make a site- or scenario-specific adjustment to the uncertainty factor for variability in worker susceptibility that is already embedded in the derivation of most OELs.
Work with medical staff to support overall cumulative risk reductions.
Non-work-related factors are not directly under the purview of the IH, and legal barriers divide work- and non-work settings. But opportunities exist for IHs to affect cumulative risks for mixed domains of exposure (work, consumer, and environment, for example). Ensuring close communication with occupational medical care providers is one way IHs can overcome these barriers. While IHs do not direct risk mitigation outside the workplace, they can educate and inform the healthcare community, who can reinforce these messages when they interact with workers.
CRAs differ from traditional risk assessments with respect to exposure potential (single stressor vs. multiple stressors), stressor type (chemical only vs. chemical and non-chemical), health endpoint (single vs. multiple; additive vs. interactive effects), and metrics by which to assess health risk (traditional vs. non-traditional metrics of exposure and effects). With these differences in mind, consider the following scenarios:
• Scenario 1:
You have been asked to conduct an industrial hygiene assessment of a new production facility. The employer wants to ensure the health and safety of the operations before employees start working at the facility.
• Scenario 2:
You have been asked to conduct an industrial hygiene assessment of an existing production facility where employees have complained of a range of health effects (headache, dizziness, nausea, eye and throat irritation, dermatitis).
How would you go about completing this assignment? What sources (stressors) do you consider? How do you measure or characterize exposures or co-exposures? What types of health effects do you consider? Where do you get your information or data? How do you determine whether there is a risk? Do you consider non-additivity of risks? What type of controls do you recommend?
Although a traditional risk assessment could answer these questions, a CRA approach would provide a much fuller characterization of the different sources of exposures and health effects, which is useful for implementing risk management controls.
Assessing cumulative risk is a complex process riddled with uncertainties and technical challenges. Implementing CRAs that fully address these issues and successfully integrate occupational and non-occupational stressors will require new frameworks and tools. Advancing CRA and applying these approaches in occupational settings largely depends on the involvement of the industrial hygiene community. The
above outlines eight activities that IHs could champion to help advance the development and use of CRA in occupational settings. CRA approaches hold great potential, but without our participation they will remain limited and not suited for characterizing complex workplace exposures.

is associate professor at the University of Cincinnati, College of Medicine, Department of Environmental Health. He can be reached at (513) 558-2407 or
is principal at E Risk Sciences, LLP. She can be reached at (303) 284-1935 or
is lead health scientist at NIOSH, Education and Information Division. He can be reached at (513) 533-8540 or
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AIHce 2016: “Applying CRA in Current Practice” (presentation, May 2016).
AIHce 2016: “Cumulative Risk Assessment Challenges and Data Needs” (presentation, May 2016).
Environmental Science & Technology
: “Cumulative Cancer Risk from Air Pollution in Houston: Disparities in Risk Burden and Social Disadvantage” (June 2008).
Environmental Science & Technology
: “Cumulative Risk Assessment (CRA): Transforming the Way We Assess Health Risks” (October 2012).
Concepts, Methods and Data Sources for Cumulative Health Risk Assessment of Multiple Chemicals, Exposures and Effects: A Resource Document
(June 2008).
EPA: Framework for Cumulative Risk Assessment (
, May 2003).
The Frank R. Lautenberg Chemical Safety for the 21st Century Act
International Journal of Environmental Research and Public Health
: “Joint Exposure to Chemical and Nonchemical Neurodevelopmental Stressors in U.S. Women of Reproductive Age in NHANES” (April 2014).
Journal of Occupational and Environmental Hygiene
: “Aggregate and Cumulative Risk Assessment—Integrating Occupational and Non-occupational Risk Factors” (December 2015 supplement).
Journal of Occupational and Environmental Hygiene
: “The Scientific Basis for Uncertainty, Safety and Modifying Factors in OEL Setting” (December 2015 supplement).
National Research Council: Science and Decisions: Advancing Risk Assessment (January 2008).
Total Worker Health
Society for Risk Analysis Annual Meeting: “Cumulative Risk Assessment for Occupational Health: Challenges and Solutions” (presentation, December 2016).
The Toxicologist
: “Cumulative Risks in Occupational Settings: A Checklist Tool to Support Decision Making” (March 2014).